Anti-beta2 glycoprotein I antibodies and platelet activation in patients with antiphospholipid antibodies: association with increased excretion of platelet-derived thromboxane urinary metabolites.
Platelet activation may contribute to the increased risk of thrombotic complications in patients with antiphospholipid antibodies (aPL). The increased urinary excretion of 11-dehydro-thromboxane B2 (11-DH-TXB2) reported in patients with lupus anticoagulant (LA) and/or anticardiolipin antibodies (aCL) reflects in vivo platelet activation. However the majority of autoimmune aPL are directed to beta2 glycoprotein I (beta2GPI) or prothrombin (II). We investigated the relationship of these antibodies with 11-DH-TXB2 urinary excretion in 34 patients with aPL. The urinary 11-DH-TXB2 was measured by EIA after extraction on octadecyl columns and purification on silica gel columns, which was validated by thin-layer chromatography/EIA procedure. A significantly increased excretion of 11-DH-TXB2 was found in aPL patients as compared to 18 normal controls (p <0.01). But no differences were seen in the excretion of 11-DH-TXB2 between patients with or without LA, or aCL. The number of patients with anti-II antibodies was too small to draw any conclusion. In contrast, patients with anti-beta2GPI antibodies IgG at moderate/high titre (group A, n = 14) had higher levels of urinary 11-DH-TXB2 than those at low titre or negative (group B, n = 20) (p = 0.01). The group A of patients presented an increase in 11-DH-TXB2 compared to controls (p <0.001), but no statistically significant difference was found between patients from the group B and normal controls. A correlation between levels of urinary 11-DH-TXB2 and titre of antibodies was only found for anti-beta2GPI-IgG (r(s) = 0.51, p <0.005). Our data show that the observed platelet activation in aPL patients is related to the presence of antibodies reacting with beta2GPI.
Forastiero
R
R
University Institute of Biomedical Sciences, Favaloro Foundation, Buenos Aires, Argentina.
Martinuzzo
M
M
Carreras
L O
LO
Maclouf
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000906:Antibodies / Q000097:blood*; D017152:Antibodies, Antiphospholipid / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D015539:Platelet Activation; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000652:urine; D053482:beta 2-Glycoprotein I
D000906:Antibodies; D017152:Antibodies, Antiphospholipid; D006023:Glycoproteins; D053482:beta 2-Glycoprotein I; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2